Sensing environmental cues is critical for bacteria to survive under different environmental conditions. This MERIT extension application proposes continued analyses ofsignal transduction components that are used by bacteria to sense alterations of oxygen tension and light intensity. One crytical oxygen and light regulated metaboUc pathway that we study is the tetrapyrrole biosynthetic pathway that synthesizes important end products heme, vitamin 312 and chlorophyll. We are actively studying how oxygen and light responding signal transduction components control synthesis ofthese tetrapyrroles with a long-term goal ofunderstanding how cells coordinate their synthesis. Our laboratory studies several oxygen and light responding receptors that are present in a wide variety of bacteria including several important pathogens where they are Implicated in controlling virulence. This proposal uses a combination of genetics, biochemistry and structural biology methodologies to obtain detailed understandings of underlying molecular mechanisms used to sense changes in oxygen tension and light intensity. We also study how this information is transmitted to transcription factors that regulate tetrapyrrole gene expression in response to oxygen and light. During the past funding period, the Pi's laboratory successfully transitioned Into the field of structural biology resulting in published crystal structures ofseveral light responding transcription factors that we study. These structural approaches are providing the first detailed understanding of how blue Ught absorption drives alteration in gene expression in bacteria. We are taking similar approaches to obtain a detailed molecular understanding of how a change in oxygen tension is sensed and how this information is used to alter cellular physiology. RELEVANCE (See instructions): This study provides molecular details of how bacteria sense changes in oxygen tension and light intensity that can affect the behaviour, survival and pathogenicity of a broad number of bacterial species.